This project concerns studies of Rocky Mountain spotted fever and other tick-borne rickettsial diseases in the United States and in certain other countries with emphasis on the ecology, identification, and characterization of rickettsiae and their relationship(s) to the respective tick vectors. Source material for experimental comparative studies is obtained through collaboration with outside agencies. The project also considers the cellular and subcellular aspects of interactions between tick-borne rickettsiae and their vectors, particularly the mechanism(s) of interference and the factors responsible for changes in the agent's pathogenicity. Isolation of rickettsiae are made from infected ticks or from bloods of patients or animals by injection into susceptible animals or cell cultures. Characterization of isolates includes serological and biochemical methods (macroagglutination, microimmunofluorescence, DNA base composition and protein (SDS-PAGE) determinations). Interactions between rickettsiae and their arthropod vectors is followed by light, fluorescence and electron microscopy of tissues from naturally or experimentally infected ticks. Tissue cultures are being used to study mechanisms of rickettsial development and infection in host cells. The white footed mouse (Peromyscus leucopus) proves to be a useful animal for monitoring spotted fever in nature. Within the distributional areas of D. variabilis, dogs do develop overt clinical spotted fever. Ticks of the I. ricinus complex were shown to be efficient vectors of R. rickettsii. There is no interference between thsee ticks' symbiotes and spotted fever rickettsiae. Efficency of the "hemolymph test" greatly improved through the use of conjugates prepared from monoclonal antibodies to R. rickettsii. Immunochemical analyses suggest that the "Swiss agent" - a spotted fever group rickettsia deteected in up to 13.5% of I. ricinus from Switzerland - represents a new species of tick-borne rickettsia for which the name Rickettsia helvetica is being proposed.